Nakano Kazumi, Watanabe Toshiki
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 4-6-1, Shirokanedai, Minatoku, Tokyo 108-8639, Japan.
Viruses. 2016 Feb 24;8(3):58. doi: 10.3390/v8030058.
Human T-cell leukemia virus type-1 (HTLV-1) Rex is a viral RNA binding protein. The most important and well-known function of Rex is stabilizing and exporting viral mRNAs from the nucleus, particularly for unspliced/partially-spliced mRNAs encoding the structural proteins essential for viral replication. Without Rex, these unspliced viral mRNAs would otherwise be completely spliced. Therefore, Rex is vital for the translation of structural proteins and the stabilization of viral genomic RNA and, thus, for viral replication. Rex schedules the period of extensive viral replication and suppression to enter latency. Although the importance of Rex in the viral life-cycle is well understood, the underlying molecular mechanism of how Rex achieves its function has not been clarified. For example, how does Rex protect unspliced/partially-spliced viral mRNAs from the host cellular splicing machinery? How does Rex protect viral mRNAs, antigenic to eukaryotic cells, from cellular mRNA surveillance mechanisms? Here we will discuss these mechanisms, which explain the function of Rex as an organizer of HTLV-1 expression based on previously and recently discovered aspects of Rex. We also focus on the potential influence of Rex on the homeostasis of the infected cell and how it can exert its function.
人类T细胞白血病病毒1型（HTLV-1）的Rex是一种病毒RNA结合蛋白。Rex最重要且广为人知的功能是稳定病毒mRNA并将其从细胞核输出，特别是对于编码病毒复制所必需结构蛋白的未剪接/部分剪接的mRNA。如果没有Rex，这些未剪接的病毒mRNA将会被完全剪接。因此，Rex对于结构蛋白的翻译以及病毒基因组RNA的稳定至关重要，进而对于病毒复制也至关重要。Rex调控广泛病毒复制和抑制的时期以进入潜伏期。尽管Rex在病毒生命周期中的重要性已被充分理解，但其实现功能的潜在分子机制尚未阐明。例如，Rex如何保护未剪接/部分剪接的病毒mRNA免受宿主细胞剪接机制的影响？Rex如何保护对真核细胞具有抗原性的病毒mRNA免受细胞mRNA监测机制的影响？在此，我们将基于之前和最近发现的Rex的相关方面来讨论这些机制，这些机制解释了Rex作为HTLV-1表达组织者的功能。我们还将重点关注Rex对受感染细胞内稳态的潜在影响以及它如何发挥其功能。
